BACKGROUND The efficacy and safety profile of tenofovir amibufenamide(TMF)in chronic hepatitis B(CHB)patients is not well-established.AIM To compare the efficacy and safety of TMF and tenofovir alafenamide(TAF)over a ...BACKGROUND The efficacy and safety profile of tenofovir amibufenamide(TMF)in chronic hepatitis B(CHB)patients is not well-established.AIM To compare the efficacy and safety of TMF and tenofovir alafenamide(TAF)over a 48-wk period in patients with CHB.METHODS A total of 215 subjects meeting the inclusion criteria were enrolled and divided into two groups:TMF group(n=106)and the TAF group(n=109).The study included a comparison of virological response(VR):Undetectable hepatitis B virus DNA levels,alanine transaminase(ALT)normalization rates,renal function parameters,and blood lipid profiles.RESULTS At 24 and 48 wk,VR rates for the TMF group were 53.57%and 78.57%,respectively,compared with 48.31%and 78.65%for the TAF group(P>0.05).The VR rates were also similar in both groups among patients with low-level viremia,both hepatitis B e antigen(HBeAg)-positive and HBeAg-negative subgroups.The TMF cohort showed ALT normalization and renal safety profiles similar to the TAF group.There was a notable increase in total cholesterol levels in the TAF group(P=0.045),which was not observed in the TMF group(P>0.05).In patients with liver cirrhosis,both groups exhibited comparable VR and ALT normalization rates and renal safety profiles.However,the fibrosis 4 score at 48 wk showed a significant reduction in the TAF group as compared to the TMF group within the liver cirrhosis subgroup.CONCLUSION Our study found TMF is as effective as TAF in treating CHB and has a comparable safety profile.However,TAF may be associated with worsening lipid profiles.展开更多
Fever and cough are the most common clinical symptoms of coronavirus disease 2019(COVID-19),but complications(such as pneumonia,respiratory distress syndrome,and multiorgan failure)can occur in people with additional ...Fever and cough are the most common clinical symptoms of coronavirus disease 2019(COVID-19),but complications(such as pneumonia,respiratory distress syndrome,and multiorgan failure)can occur in people with additional comorbidities.COVID-19 may be a new cause of liver disease,as liver profile disturbance is one of the most common findings among patients.The molecular mechanism underlying this phenomenon,however,is still unknown.In this paper,we review the most current research on the patterns of change in liver profile among patients with COVID-19,the possible explanation for these findings,and the relation to pre-existing liver disease in these patients.展开更多
The effects of sublethal levels of nuracron,dimethylphosphate-3-hydroxy-N-methyl-cis-crotonamide(0,0.625× 10-6,1.25×10-6,2.5×10-6,5.0×10-6 and 10.0×10-6) on biochemical changes(aspartate trans...The effects of sublethal levels of nuracron,dimethylphosphate-3-hydroxy-N-methyl-cis-crotonamide(0,0.625× 10-6,1.25×10-6,2.5×10-6,5.0×10-6 and 10.0×10-6) on biochemical changes(aspartate transaminase,AST,E.C.2.6.1.1;alanine transaminase,ALT;2.6.2.2;alkaline phosphatase,ALP,EC 3.1.3.1) in the organs(kidney,liver,gill) and muscle tissues of hybrid catfi sh Heterobranchus bidorsalis,♂× Clarias gariepinus,♀ [mean weight,(277.76±53.11) g SD;mean total length,(35.69±2.80) cm,SD] were studied after a 23 d exposure in a renewal bioassay under laboratory conditions.Generally,nuracron inhibited AST,ALT and ALP activities in all the exposure concentrations,with ALT activity being mostly affected.The most elicited enzyme was ALP in the kidney [(4 052.67±1610.45) IU/L],followed by AST in the muscle [(908.44±218.34) IU/L] and ALT in the liver [(160.29±73.68) IU/L].The ALP activity was 30.24 and 6.53 times greater than that of ALT and AST.The highest inhibition for AST(43.65%),ALT(47.88%) and ALP(57.98%) occurred at 10×10-6,0.625×10-6 and 2.5×10-6,respectively.The activities of the enzymes in all the organs did not show any direct relationship with the exposure concentrations of the toxicant.ALT activity in the muscle generally suffered the most compared with the other enzymes.The activities of enzymes in the liver were generally inhibited,with elevation at 5.0×10-6 for all the enzymes.The lower concentrations of nuracron(0.625 ×10-6～2.5×10-6) caused elevation in the activities of ALP,but the reverse was the case with the higher concentrations;these of AST and ALT were haphazard.The relative activities of the various enzymes in the organs showed that the order for AST was liver>muscle>kidney>gill;that for ALT:liver>kidney,muscle>gill and that for ALP:kidney>gill>liver and muscle.However,for AST and ALT the activities in the organs of the exposed fi sh peaked at 5.0×10-6 nuracron.The alteration in the activities of the enzymes indicated that the extract interfered with the Kreb's cycle intermediaries and the transamination process,and therefore could elicit negative consequences on the physiology of the fi sh,a non-target species in the aquatic environment.展开更多
Aim:We aimed to further investigate the role of hepcortespenlisimut-L(Hepko-V5 or V5),a new oral immunotherapy developed by us,for hepatocellular carcinoma(HCC)indication.Methods:The interim data from ongoing PhaseⅢp...Aim:We aimed to further investigate the role of hepcortespenlisimut-L(Hepko-V5 or V5),a new oral immunotherapy developed by us,for hepatocellular carcinoma(HCC)indication.Methods:The interim data from ongoing PhaseⅢplacebo-controlled,randomized trial were evaluated on the initial group of patients in advanced stage of HCC with emphasis on liver function and tumor marker alpha-fetoprotein levels.Additionally,an in vitro study was undertaken to elucidate the mechanism of action of V5 by measuring with flow cytometry the expression of cytokines such as IL-2,INF-γ,and TNF-αand cell activation markers CD69 and Ki67 on CD4-and CD8-positive lymphocytes isolated from peripheral blood of healthy volunteers.Results:As early as one month after treatment initiation,there was a clear improvement in alanine transaminase,aspartate transaminase,alkaline phosphatase,and bilirubin levels among HCC patients who received daily dose of V5,but not in the placebo group.Additionally,alpha-fetoprotein(AFP)levels among V5 recipients decreased,while in the ;placebo group they rose.Clinical results are in line with in vitro observations indicating immune activation,as evidenced by many-fold enhancement of CD69,Ki67,and INF-γexpression and at the same time marked anti-inflammatory effect resulting in 10-fold decrease in TNF-αoutput and lack of influence on IL-2 production.Conclusion:Hepcortespenlisimut-L,a tableted oral formulation derived from heat-inactivated pooled blood of patients with HCC and viral hepatitis shows beneficial clinical effect,as demonstrated by improvement in liver function and reduction of tumor marker AFP levels.These correlate with in vitro observations showing potent activation of the immune response and pronounced oral tolerance effect.展开更多
基金Supported by National Natural Science Foundation of China,No.82170640,No.81974080Natural Science Foundation of Hunan Province,No.2022JJ30954。
文摘BACKGROUND The efficacy and safety profile of tenofovir amibufenamide(TMF)in chronic hepatitis B(CHB)patients is not well-established.AIM To compare the efficacy and safety of TMF and tenofovir alafenamide(TAF)over a 48-wk period in patients with CHB.METHODS A total of 215 subjects meeting the inclusion criteria were enrolled and divided into two groups:TMF group(n=106)and the TAF group(n=109).The study included a comparison of virological response(VR):Undetectable hepatitis B virus DNA levels,alanine transaminase(ALT)normalization rates,renal function parameters,and blood lipid profiles.RESULTS At 24 and 48 wk,VR rates for the TMF group were 53.57%and 78.57%,respectively,compared with 48.31%and 78.65%for the TAF group(P>0.05).The VR rates were also similar in both groups among patients with low-level viremia,both hepatitis B e antigen(HBeAg)-positive and HBeAg-negative subgroups.The TMF cohort showed ALT normalization and renal safety profiles similar to the TAF group.There was a notable increase in total cholesterol levels in the TAF group(P=0.045),which was not observed in the TMF group(P>0.05).In patients with liver cirrhosis,both groups exhibited comparable VR and ALT normalization rates and renal safety profiles.However,the fibrosis 4 score at 48 wk showed a significant reduction in the TAF group as compared to the TMF group within the liver cirrhosis subgroup.CONCLUSION Our study found TMF is as effective as TAF in treating CHB and has a comparable safety profile.However,TAF may be associated with worsening lipid profiles.
文摘Fever and cough are the most common clinical symptoms of coronavirus disease 2019(COVID-19),but complications(such as pneumonia,respiratory distress syndrome,and multiorgan failure)can occur in people with additional comorbidities.COVID-19 may be a new cause of liver disease,as liver profile disturbance is one of the most common findings among patients.The molecular mechanism underlying this phenomenon,however,is still unknown.In this paper,we review the most current research on the patterns of change in liver profile among patients with COVID-19,the possible explanation for these findings,and the relation to pre-existing liver disease in these patients.
文摘The effects of sublethal levels of nuracron,dimethylphosphate-3-hydroxy-N-methyl-cis-crotonamide(0,0.625× 10-6,1.25×10-6,2.5×10-6,5.0×10-6 and 10.0×10-6) on biochemical changes(aspartate transaminase,AST,E.C.2.6.1.1;alanine transaminase,ALT;2.6.2.2;alkaline phosphatase,ALP,EC 3.1.3.1) in the organs(kidney,liver,gill) and muscle tissues of hybrid catfi sh Heterobranchus bidorsalis,♂× Clarias gariepinus,♀ [mean weight,(277.76±53.11) g SD;mean total length,(35.69±2.80) cm,SD] were studied after a 23 d exposure in a renewal bioassay under laboratory conditions.Generally,nuracron inhibited AST,ALT and ALP activities in all the exposure concentrations,with ALT activity being mostly affected.The most elicited enzyme was ALP in the kidney [(4 052.67±1610.45) IU/L],followed by AST in the muscle [(908.44±218.34) IU/L] and ALT in the liver [(160.29±73.68) IU/L].The ALP activity was 30.24 and 6.53 times greater than that of ALT and AST.The highest inhibition for AST(43.65%),ALT(47.88%) and ALP(57.98%) occurred at 10×10-6,0.625×10-6 and 2.5×10-6,respectively.The activities of the enzymes in all the organs did not show any direct relationship with the exposure concentrations of the toxicant.ALT activity in the muscle generally suffered the most compared with the other enzymes.The activities of enzymes in the liver were generally inhibited,with elevation at 5.0×10-6 for all the enzymes.The lower concentrations of nuracron(0.625 ×10-6～2.5×10-6) caused elevation in the activities of ALP,but the reverse was the case with the higher concentrations;these of AST and ALT were haphazard.The relative activities of the various enzymes in the organs showed that the order for AST was liver>muscle>kidney>gill;that for ALT:liver>kidney,muscle>gill and that for ALP:kidney>gill>liver and muscle.However,for AST and ALT the activities in the organs of the exposed fi sh peaked at 5.0×10-6 nuracron.The alteration in the activities of the enzymes indicated that the extract interfered with the Kreb's cycle intermediaries and the transamination process,and therefore could elicit negative consequences on the physiology of the fi sh,a non-target species in the aquatic environment.
基金This study would never have had a chance to succeed if we did not receive the financial contribution from our former patient with terminal HCC,Dr.Steve Kramer-now in complete remission since 2014-and his spouse Jane Kramer,who as our genuine friends generously supported our effort over many years.Additional support was provided by several other patients who contributed extra in addition to regular payment for Hepko-V5.They were not involved in clinical study design,collection,analysis and interpretation of data.
文摘Aim:We aimed to further investigate the role of hepcortespenlisimut-L(Hepko-V5 or V5),a new oral immunotherapy developed by us,for hepatocellular carcinoma(HCC)indication.Methods:The interim data from ongoing PhaseⅢplacebo-controlled,randomized trial were evaluated on the initial group of patients in advanced stage of HCC with emphasis on liver function and tumor marker alpha-fetoprotein levels.Additionally,an in vitro study was undertaken to elucidate the mechanism of action of V5 by measuring with flow cytometry the expression of cytokines such as IL-2,INF-γ,and TNF-αand cell activation markers CD69 and Ki67 on CD4-and CD8-positive lymphocytes isolated from peripheral blood of healthy volunteers.Results:As early as one month after treatment initiation,there was a clear improvement in alanine transaminase,aspartate transaminase,alkaline phosphatase,and bilirubin levels among HCC patients who received daily dose of V5,but not in the placebo group.Additionally,alpha-fetoprotein(AFP)levels among V5 recipients decreased,while in the ;placebo group they rose.Clinical results are in line with in vitro observations indicating immune activation,as evidenced by many-fold enhancement of CD69,Ki67,and INF-γexpression and at the same time marked anti-inflammatory effect resulting in 10-fold decrease in TNF-αoutput and lack of influence on IL-2 production.Conclusion:Hepcortespenlisimut-L,a tableted oral formulation derived from heat-inactivated pooled blood of patients with HCC and viral hepatitis shows beneficial clinical effect,as demonstrated by improvement in liver function and reduction of tumor marker AFP levels.These correlate with in vitro observations showing potent activation of the immune response and pronounced oral tolerance effect.
